Additional Disorders Detected by MS/MS Screening

Amino acid disorders
    Argininosuccinic aciduriaA disorder of the urea cycle. Episodes of hyperammonemia produce acute intoxication. The major symptoms include mental retardation, failure to thrive, liver dysfunction, unusual hair (trichorrhexis nodosa), and seizures.
    CitrullinemiaA disorder of the urea cycle. Episodes of hyperammonemia produce coma and seizures. The major symptoms include changes in sensorium (irritability, lethargy), seizures, ataxia, and mental retardation.
    HypermethioninemiaCan be seen in a variety of conditions. It is found in conjunction with homocystinuria and tyrosinemia. Neonatal hypermethioninemia can occur in preterm infants or be attributable to neonatal hepatitis or a combination of factors.
FAO disorders
    Carnitine/acylcarnitine translocase deficiencyMajor symptoms are fasting hypoglycemia with seizures and coma, cardiomyopathy, arrhythmias, muscle weakness, and hepatomegaly/abnormal liver function.
    3-Hydroxy long-chain acyl-coenzyme A dehydrogenase (LCHAD) deficiencyResults in an inability of the body to break down fatty acids into a usable energy source. LCHAD deficiency can present as hypoglycemia, lethargy, SIDS, hypotonia, and cardiomyopathy.
    MCAD deficiencyCan cause recurrent episodes of hypoglycemia, failure to thrive, persistent vomiting, hepatomegaly, and rhabdomyolysis. Acute episodes are usually associated with concurrent illness or fasting and occur in infancy or early childhood.
    Multiple acyl-coenzyme A dehydrogenase deficiency (also known as glutaric acidemia-type II)Often associated with unexplained death in neonates. Other features include respiratory distress, hypotonia, unusual odor (described as “sweaty feet”) and liver dysfunction.
    Neonatal carnitine palmitoyl transferase deficiency-type IISymptoms include hypoketotic hypoglycemia with seizures and coma, cardiac arrhythmia, cardiomyopathy, and hepatopathy.
    Short-chain acyl-coenzyme A dehydrogenase (SCAD) deficiencyPatients with SCAD deficiency have failure to thrive, developmental delays/hypotonia, metabolic acidosis, recurrent emesis, and a lipid-storage myopathy.
    Short-chain hydroxy acyl-coenzyme A dehydrogenase deficiencyThe major symptom is hypoketotic hypoglycemia.
    Trifunctional protein deficiencyCan present as skeletal myopathy, cardiomyopathy, or SIDS.
    Very long-chain acyl-coenzyme A dehydrogenase deficiencySymptoms are similar to other FAO defects.
Organic acid disorders
    3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiencyThis enzyme catalyzes the final step of leucine catabolism and plays a key role in ketone body formation. The major clinical features are metabolic acidosis and hypoglycemia. Unexplained fevers can occur. Encephalopathy (somnolence, coma, and malaise) and hepatopathy are common. SIDS may occur.
    Glutaric acidemia type IResults from an inherited defect in the degradation of lysine and tryptophan. Macrocephaly with an increase in the size of the extra cerebral fluid spaces occurs before the onset of any neurologic symptoms. Neurologic disease usually presents later in infancy with tonal abnormalities and choreoathetosis secondary to basal ganglia injury.
    Isovaleric acidemiaThis is a disorder of branched-chain amino acid metabolism that results in recurrent episodes of emesis, dehydration, and severe metabolic acidosis. Other symptoms include anorexia, listlessness, lethargy, neuromuscular irritability, and hypothermia. Acute episodes are associated with concurrent illnesses or high dietary protein intake.
    Methylmalonic acidemiaAn increase in methylmalonic acid can be seen with a variety of conditions. Transient increases in methylmalonic acid can be detected in otherwise healthy infants. Symptoms can include failure to thrive, episodic dehydration, and hypotonia. A variety of central nervous system changes (dystonia, dysphagia, and dysarthria) can occur. Infants with methylmalonic acidemia have been noted to have distinct facial dysmorphism.
    Propionic acidemiaSymptoms are usually episodic emesis, dehydration, and metabolic acidosis. Hematologic abnormalities such as neutropenia, thrombocytopenia, and hypogammaglobulinemia are common. Mental retardation is a consistent feature, and most patients exhibit intolerance to dietary protein.
    Multiple-coenzyme A carboxylase deficiencyThis is a deficiency of the enzyme that attaches biotin to enzyme proteins that then results in multiple secondary enzyme deficiencies. Symptoms can be linked to deficiencies of the individual enzymes. Recurrent episodes of emesis, metabolic acidosis, and seizures can occur.
    Other organic acidemias detected by MS/MS screening2-Methylbutyryl-coenzyme A dehydrogenase deficiency, 3-methylcrotonyl-coenzyme A carboxylase deficiency, 3-methylglutaconyl-coenzyme A hydratase deficiency, mitochondrial acetoacetyl-coenzyme A thiolase deficiency (3-ketothiolase deficiency)
Other abnormal profilesAbnormal results may be found on MS/MS screening secondary to hyperalimentation, liver disease, or contamination of the specimen. Also, treatment with medium-chain triglyceride oil, benzoate, valproate, or pyvalic acid can produce abnormal results.
  • SIDS indicates sudden infant death syndrome.